Abstract GS5-01: Residual cancer burden after neoadjuvant therapy and long-term survival outcomes in breast cancer: A multi-center pooled analysis

• Published in: Cancer research (Chicago, Ill.) Ill.), 2020-02, Vol.80 (4_Supplement), p.GS5-01-GS5-01
• Main Authors: Yau, Christina, van der Noordaa, Marieke, Wei, Jane, Osdoit, Marie, Reyal, Fabien, Hamy, Anne-Sophie, Lae, Marick, Martin, Miguel, del Monte, Maria, Boughey, Judy C, Gould, Rebekah, Wesseling, Jelle, Steenbruggen, Tessa, van Seijen, Maartje, Sonke, Gabe, Edge, Stephen, Sammut, Stephen-John, Provenzano, Elena, Abraham, Jean, Hall, Peter, Graham, Ashley, Mackintosh, Lorna, Cameron, David, Wang, Alice, Sharma, Priyanka, Cole, Kimberly, Pusztai, Lajos, Kim, Mi-Ok, van ‘t Veer, Laura, Esserman, Laura, Symmans, W. Fraser
• Format: Article
• Language: English
• ISSN: 0008-5472; 1538-7445
• DOI: 10.1158/1538-7445.SABCS19-GS5-01

Background: Recent studies have demonstrated independent validation of the prognostic relevance of residual cancer burden (RCB) after neoadjuvant chemotherapy. However, a pooled subject-level analysis of multiple cohorts is needed to determine estimates of long-term prognosis for each class of RCB in each phenotypic subtype of breast cancer (BC) to better inform on patient outcomes. Also, a pooled subject-level analysis allows more detailed analyses of generalizability of the prognostic meaning of RCB assessments in a broader experience of practice settings. Method: Subject-level RCB results, with relevant clinical and pathologic stage, tumor subtype and grade, demographic, treatment and follow-up data from 11 institutes/trials are being collected for combined analysis. The association between the continuous RCB index and event-free survival (EFS), and distant recurrence free survival (DRFS) were assessed using mixed effect Cox models with the incorporation of random RCB coefficients to account for between-study heterogeneity. We will also allow for differences in baseline hazard across biological BC subtypes and, if needed, across studies as well. In addition to this stratified mixed effect model, a multivariate analysis adjusting for age, T-category, nodal status and grade was performed within each subtype. In addition, mixed effect Cox models will be employed to evaluate association between RCB index with EFS and DRFS within each HR/HER2 subtype. Kaplan Meier estimates of EFS and DRFS at 5 and 10 years were computed for each RCB class within subtype. Results: We analyzed subject-level data from 9 institutes/trials representing 4077 patients currently available from an anticipated final total of 4,800 patients (to be presented at the meeting). There were 950 EFS and 876 DRFS events during follow up (median 65 months, IQR: 70 months). RCB index (continuous) was independently prognostic within each subtype: HR+/HER2- (EFS HR (per unit increase in RCB index) =1.64, 95%CI 1.48-1.82; DRFS HR=1.68, 1.51-1.87), HR+/HER2+ (EFS HR=1.80, 1.57-2.05; DRFS HR=1.93, 1.67-2.24), HR-/HER2+ (EFS HR=2.15, 1.76-2.62; DRFS HR=2.10, 1.77-2.50), and HR-/HER2- (EFS HR=2.05, 1.89-2.22; DRFS HR=2.16, 1.90-2.46); and remained prognostic in multivariate models adjusting for age, grade, and clinical T and N stage at diagnosis. Table 1 contains the response rate and estimated EFS at 5 years and 10 years for each RCB class within each HR/HER2 phenotype (DRFS results were similar). Co